The proposed experiments focus on structures in the brain stem which play important roles in antinociception, on their organization and interrelationship(s) in the brain stem, and on the neurotransmitters involved. The overall objective of the proposed experiments is to clarify the interactions in the brain stem of structures contributing to opioid- and stimulation-produced antinociception and the neurotransmitters in the brain and spinal cord which mediate both opioid- and stimulation-produced antinociception. The specific aims include: (1) quantitative evaluation and characterization of antinociception produced by morphine and focal electrical stimulation given at identical sites in brain. The brain areas in focus include the lateral hypothalamus, midbrain periaqueductal gray and adjacent reticular formation, the norepinephrine-containing pontine cell groups (A7/parabrachial area, A6 and A5 cell groups), the rostroventral medulla and the medullary lateral reticular nucleus/A1 area. (2) Evaluation of the contributions of areas in the brain stem interposed between the hypothalamus or midbrain and the spinal cord in the antinociception produced by drugs or electrical stimulation given in the hypothalamus or midbrain. And (3) evaluation of neurotransmitters at brain stem relays between the hypothalamus or midbrain and the spinal cord which mediate the descending antinociception produced by drugs or stimulation given in these rostral structures. A variety of approaches will be employed to generate converging pharmacologic, behavioral, neurochemical and electrophysiologic evidence relative to the working hypothesis that functionally important relays between rostral structures in the brain and the spinal cord play important roles in descending antinociceptive mechanisms. These experiments will clarify the organization in the brain stem of structures important to antinociception and the neurotransmitters by which these effects are mediated. Quantitative investigation of the areas in brain selected and elucidation of the transmitters involved will lead to better understanding of the centrifugal modulation of pain.